Study of the effect of pentoxifylline in hepatlc ischemia-reperfusion injury in albino rats

ABSTRACT

Hepatic ischemia reperfusion injury [IRI] is a common pathological process of traumatic surgical diseases in the liver, liver transplantation, shock and infection. Inflammatory mediators are implicated in the pathogenesis of IRI. Pentoxifylline [PTX] is a derivative of methylxanthine, acts as a phosphodiesterase inhibitor and therapy elevares the levels of cAMP. Interest in PTX has been recently reawakened because of its reported suppressive action on immune functions, particularly on cytokine production. It has been shown to be beneficial in organ transplantation. Pentoxifyllin probably acts primarily by inhibiting tumor necrosis factor-alpha [TNF-alpha]. We hypothesized that PTX treatment would attenuate hypoxic ischemic liver injury. Thirty-six male albino rats were used throughout this experiment. Animals were divided into 2 main groups; each comprised 18 rats [sham-operated and IRI groups]. Group [1] sham-operated [exposed to anesthesia and laparotomy], this group is subdivided into 3 equal subgroups. Subgroup 1A Sham-operated received daily intra-gastric saline, subgroup IB sham-operated +PTX [8mg/kg/day] for 6 successive weeks before exposure to anesthesia and laparotomy, subgroup IC as IB but received PTX [16mg/kg/day]. Group [II] IRI group, divided into 3 equal subgroups, sub- group llA received intra-gastric saline for 6 weeks before the induction of IRI ,subgroup 116, received 8mg/kg/day PTX intra-gastrically for 6 weeks before induction of IRI, subgroup IIB, recieved 8mg/kg/day PTX intra-gastrically for 6 weeks before induction of IRI, subgroup IIC, received PTX [16 mg/kg/day] before induction of IRI. It was found that IRI produced significant increase in plasma alanine transaminase [ALT], malondialdehyde [MDA], TNF-alpha and hepatic tissue calcium content as compared to sham-operated animal groups. Intra- gastric administration of PTX in the small or large doses for 6 weeks before induction of IRI produced no significant change in the hepatic tissue calcium, plasma MDA, ALT and plasma TNF-alpha as compared to sham control group, but it produced significant decrease as compared to IRI control group. On the light of the present study, these preliminary results with PTX are encouraging to recommend further human studies in hepatic patients especially whom are given PTX for associated cardiovascular problems